Alzheimer's disease (AD) is a degenerative brain disorder characterized clinically by progressive loss of memory, cognition, reasoning,judgement and emotional stability that gradually leads to profound mental deterioration and ultimately death. AD is the leading cause of dementia in the elderly, today affecting 4-5 million Americans, which is expected to increase to 8-10 million Americans within the next 25 years. Currently there is no effective biochemical test for AD and/or to monitor its progression. Recent studies indicate that the beta-amyloid protein (Abeta) of AD is maintained in biological fluids in a soluble state by an unknown mechanism. Implicated proteins which may contribute to such Abeta solubility in biological fluids include apolipoproteins, albumin and laminin. In our initial studies, we have encountered a new Abeta-binding protein in serum and cerebrospinal fluid (CSF) of AD and normal aged patients' (designated as P400). Our preliminary data indicate that P400 in human serum and CSF binds tightly to Abeta and is decreased substantially in serum derived from AD patients in comparison to normal aged controls. These initial studies suggest the detection of a new Abeta-binding protein which may be responsible for maintenance of Abeta solubility in biological fluids. The overall objective of this phase I SBIR proposal is to determine 1) the identity of P400, 2) P400's effects on Abeta-binding and Abeta- fibrillogenesis, and 3) P400's potential as a diagnostic indicator of AD. In a future phase II proposal, it is anticipated that studies will be implemented to determine the mechanism of how P400 may maintain Abeta solubility and will involve the design of potential anti-amyloid therapeutics based on this new knowledge. In addition, if P400 proves to be a potential biochemical marker for AD as determined by phase I, it will be assessed in a much larger study to determine if a new blood and/or CSF test for AD has been found. Identification of a new protein which may be a specific indicator for AD should allow for both novel therapeutic and diagnostic approaches in the future. PROPOSED COMMERCIAL APPLICATIONS: Alzheimer's disease (AD) currently affects 4-5 million Americans, at an estimated costs of $80-$100 billion. Currently, there is no reliable biochemical test or indicator for AD and/or its progression. It is estimated that the current world-wide market for such a biochemical indicator for AD and/or its progression is $150 million US dollars. If we capture 10-20% of that market, potential revenue for such a diagnostic test would be $15-30 million US dollars. In addition, potential licensing opportunities for the development of this biochemical test are anticipated to yield substantial revenues in the future.